The Role of Neuron Cell Death on Outcome
Due to the focus on pathological changes in periventricular white matter, relatively little was known about the effects of hydrocephalus on gray matter prior to the mid-1980s. Since then, most of the information has been obtained from studies of the cerebral cortex, leaving assessments of subcortical tissue open for future investigation. Technical difficulties compound the necessary quantitative analyses, because the stretching and distortion of tissue volume must be taken into account when determining neuronal density.

Although the disruption of cellular layers in the cerebral cortex is remarkable during hydrocephalus, cell death may be less important than previously thought. While quantitative studies have demonstrated significant reductions in neurons from deep cortical layers in rats with severe congenital hydrocephalus, and some degenerating neurons have been observed ultrastructurally in humans, the results from shunting experiments suggest that neuron death is either preventable or not appreciable.

This idea gains further support from the recent work of Dr. Marc Del Bigio, who showed that the number of neurons dying from apoptosis, a genetically-programmed form of cell death, was not dramatic. Nevertheless, it is still not clear if an appreciable amount of neurons could be dying from necrosis, a form of cell death that results from direct trauma to neurons. Axonal degeneration, probably from axotomy (cutting the axon), is a common feature of hydrocephalus, and could cause the death of the "parent" neuron.

Our ongoing studies should determine not only the type of cell death that occurs during hydrocephalus, but most importantly, whether or not the loss of neurons can cause significant neurological deficits
Neurons from the cerebral cortex of a hydrocephalic animal. The dark cells are "suffering" and may or may not go on to degenerate. It is important to note that they reside next to normal neurons (arrow) that could compensate for the loss of their neighbors.